SJL strain mice spontaneously develop lymphomas which, upon transplantation in syngeneic mice, can grow either as indolent or aggressive tumors. Whereas indolent tumors are at constant risk of conversion to the aggressive type, aggressive tumors maintain their aggressiveness. The increase in aggressiveness of SJL lymphomas correlates with absence of H-2Ds, class I major histocompatibility complex (MHC) antigen from the tumor cell surface. It is, herein, proposed to test the hypothesis that the increased aggressiveness of H-2Dsnegative (D-) SJL lymphomas may, in part, be attributed to: 1) deficient killing of D-tumor cells by cytotoxic T lymphocytes (CTL) as a consequence of preferential recognition of tumor antigen by CTL in association with H-2Ds; 2) deficient recognition and/or killing of D-tumor cells by natural killer cells, or; 3) a greater sensitivity of D-tumor cells to the stimulatory influence of lymphokines synthesized as a consequence of the T cell proliferation which accompanies the growth of most SJL lymphomas or a greater propensity of D-lymphomas to induce synthesis of such lymphokines. Since a similar increase in aggressiveness is seen during the progression of some human lymphomas, it is hoped that the results of this study will spur investigation of loss of class I MHC antigen as a potential prognostic indicator in humans. (MI)